1. Field of the Invention
The present invention relates to a sensing device for sensing a substance to be sensed contained in a sample solution based on an oscillation frequency of a piezoelectric resonator such as a quartz-crystal resonator.
2. Description of the Related Art
As a sensing device for sensing and measuring a trace substance contained in a sample solution, there has been known one which uses a quartz-crystal sensor being a piezoelectric sensor. As this type of sensing device, one that detects a substance to be sensed while letting a sample solution flow, as disclosed in Patent Document 1, has been known. Meanwhile, as a quartz-crystal sensor, there has been known a quartz-crystal sensor of twin sensor type capable of reducing an influence of an external factor of measurement environment such as a temperature, for instance (Patent Document 2). In this quartz-crystal sensor, an oscillation area for measurement and an oscillation area for reference are formed on a quartz-crystal piece, and on a front surface of the oscillation area for measurement, there is formed an absorption layer formed of a biological substance or the like. Accordingly, since only the oscillation area for measurement is affected by a mass change caused by an absorption of a substance to be sensed, by subtracting an oscillation frequency taken out from the oscillation area for reference from an oscillation frequency taken out from the oscillation area for measurement, it is possible to obtain a highly accurate measured result from which the external factor is removed.
Here, the applicant of the present application has been studying a method of reducing a height of a reaction channel (distance from a front surface of a quartz-crystal resonator and an opposing surface within a case body), as an example of a method of performing measurement of trace substance with higher sensitivity and higher accuracy. For example, even if the height of the reaction channel corresponds to a small size of 1 mm, a ratio in which an antigen reacts with an antibody in a liquid flow on the opposing surface side is smaller than a ratio in which an antigen reacts with an antibody in a liquid flow on the quartz-crystal resonator side. For this reason, a ratio of a substance to be sensed which is absorbed in an absorption layer, out of the substance to be sensed contained in a supplied sample solution is small, and thus it cannot be said that it is advantageous in terms of both sensitivity and accuracy.
Accordingly, it can be considered that by setting the distance between the front surface of the quartz-crystal sensor and the opposing surface, namely, the height of the reaction channel to 0.2 mm or less, for example, the ratio of sample solution which is brought into contact with the absorption layer of a quartz-crystal piece or flows in the vicinity of the absorption layer, out of the supplied sample solution, is increased. By setting as above, an amount of substance to be sensed contained in the sample solution that is absorbed in the absorption layer is increased, and an amount of substance to be sensed that is discharged without being absorbed is decreased, which leads to enhance the measurement sensitivity and accuracy of the substance to be sensed. Further, the reduction in the height of the reaction channel leads to reduce a volume of the reaction channel, which enables to reduce an amount of sample solution required for the measurement, so that in terms of elimination of necessity of diluting the sample solution as well, the reduction in height contributes to the enhancement in the measurement sensitivity and accuracy of the substance to be sensed.
However, when a case in which the height of the reaction channel is made very small as above is applied to the aforementioned quartz-crystal sensor of twin sensor type, because of a difference in wettability between the two oscillation areas (for example, the hydrophilic oscillation area for measurement having the absorption layer formed of the biological substance or the like formed on the front surface thereof and the hydrophobic oscillation area for reference made of gold), an air bubble is not discharged and remained on the side of the oscillation area with higher hydrophobic property out of the two oscillation areas, which is, for example, the oscillation area for reference made of gold, as shown in FIG. 34, which makes it difficult to conduct the measurement with high reliability.
Further, there is a flow cell system in which a flow cell including supply and discharge channels of a sample fluid (sample solution) is provided to a sensing device, a piezoelectric resonator is disposed in a space formed in the flow cell, and the sample fluid is continuously supplied to a surface of the piezoelectric resonator by using the space as a reaction channel of the sample fluid (Patent Document 3, for example). Since a flow-cell sensing device can continuously supply a sample fluid, it is easy to stabilize a frequency characteristic, and further, a displacement of liquids can be smoothly conducted, so that an amount of sample fluid used can be reduced, which is advantageous.
In such a flow-cell sensing device, it is required to perform operation to dispose a piezoelectric sensor on a flow cell, and mount the piezoelectric sensor to the sensing device by connecting a terminal of electrode of a piezoelectric resonator provided to the piezoelectric sensor to an oscillator circuit. Conventionally, such a mounting operation has been conducted by a user by hand, but, in order to avoid a phenomenon such that a good sensing result cannot be obtained due to a mounting failure and to reduce a period of time of the mounting operation, an automation of process of mounting the piezoelectric sensor has been required.
In Patent Document 4, there is described a sensing device in which a main body part (first part) including a casing in which a piezoelectric sensor is to be inserted (a unit of housing a sensor element) is disposed between opening/closing parts capable of being opened/closed in a horizontal direction (which are described as “second parts” in the specification of Patent Document 4, and in the following citation of Patent Document 4, a name in the specification is described within parentheses). In the casing, there is formed an opening portion at a position corresponding to a position of a piezoelectric resonator of the piezoelectric sensor inserted in the casing, and on one side of the opening/closing parts, a flow cell (flow cell element) capable of being fitted in the opening portion is provided. Further, it is designed such that by moving, after inserting the piezoelectric sensor in the aforementioned casing, the opening/closing parts to a closed position so as to sandwich the main body part from the left and right, the flow cell is fitted in the opening portion of the casing, which enables to supply a sample fluid to the piezoelectric resonator.
In the sensing device described in Patent Document 4, although the operation to connect the flow cell to the casing that houses the piezoelectric sensor is automated, there is no description regarding a method of disposing the piezoelectric sensor in the casing. Therefore, when the operation is conducted by hand, there still remains problems such as an operation loss and a mounting failure.
[Patent Document 1] Japanese Patent Application Laid-open No. 2008-58086 (paragraph 0014, FIG. 11 and FIG. 13)
[Patent Document 2] Japanese Patent Application Laid-open No. 2007-108170
[Patent Document 3] Japanese Patent Application Laid-open No. H11-183479: paragraph 0002, paragraph 0024, and FIG. 2
[Patent Document 4] Translated National Publication of Patent Application No. 2006-510901: Claim 1, paragraph 0026, FIG. 2, FIG. 4 and FIG. 7